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FeNO can be measured in children aged 7 years and older with high success rates after coaching them through the procedure. FeNO can play an important role in the diagnosis and management of their disease.1 In several recent studies (Peirsman 2014, Petsky 2014, Mahr 2013), asthma therapy directed by FeNO has been shown to reduce asthma exacerbations in children when compared with symptom-based care or usual care.2-4
Use caution and clinical judgement when evaluating a single FeNO value without any previous measurements. Evaluate all clinical data (symptoms, spirometry, ICS dosing, medication adherence and other information) before making any treatment decisions.
FeNO is not a replacement for spirometry. FeNO measures airway inflammation, while spirometry measures airflow limitation. They both provide important information about different aspects of the disease. For example, FeNO can provide information on the level of underlying airway inflammation, but it cannot tell you the degree of airflow obstruction, which is important to know when asthma is more severe.
However, for treatment optimization, recent publications indicate that adjusting ICS dose according to FeNO value gives reductions in exacerbations up to 50%.2,5 So FeNO measurement is advised in addition to spirometry.2,5,6
There are other causes of elevated exhaled nitric oxide. After carefully excluding asthma with other tests, significant allergic rhinitis and eczema should be considered. Also, food allergies and bowel diseases have been reported to increase exhaled NO. A diet rich in nitrate-containing foods may also raise exhaled NO.7-9
In one study (Anderson 2012), the t1/2 for FeNO after starting treatment with ICS was 2.5 to 3 days. FeNO had reached a new plateau by 2 weeks.10 Thus, rechecking FeNO 10-14 days after starting ICS would be the earliest we would recommend.
This is unknown, as long-term studies looking at variation in FeNO and its time course in relation to an exacerbation have not been performed.11
Results from spirometry poorly correlate with FeNO since spirometry measures airway obstruction and FeNO measures airway inflammation.2,5 It is beneficial to measure inflammation because it will precede lung function changes and symptoms.12
Generally, patients seen by asthma specialists should have a baseline FeNO measurement, particularly those who are not well controlled. Once treatment with ICS is started, FeNO should be monitored according to the patient’s symptoms while optimising the ICS dose. In studies that showed a reduction in exacerbations, measuring FeNO every 2 to 4 months and titrating ICS until FeNO was in the low/normal range resulted in nearly 50% reduction in exacerbations when compared with protocols that used symptom-based treatments (ACQ) or usual care.2-5
FeNO values in the intermediate range (25-50 ppb) should be interpreted cautiously and with reference to the clinical context (ie, ICS dose, patient adherence, etc).
FeNO will not reflect the level of mast cells. While mast cells can and do produce IL-13 that can stimulate epithelial cells to transcribe iNOS and produce more NO, other immune mediator cells also function in this capacity. Antihistamines will not affect this function of mast cells and thus will not alter NO production. Antileukotriene receptor antagonists have not been shown to have definitive effects on exhaled nitric oxide in patients with atopic asthma, though there are some theoretical reasons they might.13
References: 1. Malinovschi, A, Janson, C, Borres M. Simultaneously increased fraction of exhaled nitricoxide levels and blood eosinophil counts relate to increased asthma morbidity. J Allergy Clin Immunol. 2016 Nov; 138(5):1301-1308. 2. Peirsman EJ, Carvelli TJ, Hage PY, et al. Exhaled nitric oxide in childhood allergic asthma management: a randomised controlled trial. Pediatr Pulmonol. 2014;49(7):624-631. 3. Petsky H. Exhaled nitric oxide in children with asthma. Respiratory care nurse’s perspective. Indian Pediatr. 2014;51(2):102-103. 4. Mahr TA, Malka J, Spahn JD. Inflammometry in pediatric asthma: a review of fractional exhaled nitric oxide in clinical practice. Allergy Asthma Proc. 2013;34(3):210-219. 5. Syk J, Malinovschi A, Johansson G, et al. Anti-inflammatory treatment of atopic asthma guided by exhaled nitric oxide: a randomized, controlled trial. J Allergy Clin Immunol Pract. 2013;1(6):639-648. 6. Smith AD, Cowan JO, Brassett KP, Herbison P, Taylor DR. Use of exhaled nitric oxide measurements to guide treatment in chronic asthma. N Engl J Med. 2005;352(21):2163-2173. 7. Donohue JF, Jain N. Exhaled nitric oxide to predict corticosteroid responsiveness and reduce asthma exacerbation rates. Respir Med. 2013;107(7):943-952. 8. Alving K, Malinovschi A. Basic aspects of exhaled nitric oxide. Eur Respir Mon. 2010;49:1-31. 9. Quenon L, Hindryckx P, De Vos M, et al. Hand-held fractional exhaled nitric oxide measurements as a non-invasive indicator of systemic inflammation in Crohn’s disease. J Crohn Colitis. 2013;7:644-648. 10. Anderson WJ, Short PM, Williamson PA, Lipworth BJ. Inhaled corticosteroid dose response using domiciliary exhaled nitric oxide in persistent asthma. Chest. 2012;142(6):1553-1561. 11. Beck-Ripp J, Griese M, Arenz S, Köring C, Pasqualoni B, Bufler P. Changes of exhaled nitric oxide during steroid treatment of childhood asthma. Eur Respir J. 2002;19(6):1015-1019. 12. Zeiger RS, Schatz M, Zhang F, et al. Elevated exhaled nitric oxide is a clinical indicator of future uncontrolled asthma in asthmatic patients on inhaled corticosteroids. J Allergy Clin Immunol. 2011; 128 (2):412-414. 13. Bjermer L, Alving K, Diamant Z, et al. Current evidence and future research needs for FeNO measurement in respiratory diseases. Respir Med. 2014;108(6):830-841.